Lower extremity peripheral arterial disease (PAD) is a major cause of morbidity and mortality in the U.S., with an estimated prevalence up to 20% in those over 75 years. Gadolinium-enhanced MR angiography (MRA) has emerged as a highly accurate, less invasive approach that has replaced DSA in many diagnostic settings. Recently, gadolinium administration has been linked to the development of nephrogenic systemic fibrosis (NSF) in patients with renal insufficiency. Development of MRA techniques that do not require gadolinium contrast is vitally important for the 8 - 38% of PAD patients with renal insufficiency. A promising non- contrast MRA technique, ECG-FSE, uses an ECG-triggered 3D fast spin echo sequence, which exploits differences in arterial and venous flow during the cardiac cycle. From preliminary experience with ECG-FSE, we identified key factors that compromise image quality in clinical patients about 50% of the time: (a) application of a single set of imaging parameters to both legs despite differences in flow characteristics and (b) relatively long FSE acquisition windows, which contribute to image artifacts. In this proposal, we describe a new approach, VFA-FSE, which incorporates a series of technical improvements including use of variable flip angle FSE, parallel imaging, and separate sagittal acquisitions for each leg to overcome these limitations. Our aims are (1) To systematically develop, test, and refine peripheral vascular 3D VFA-FSE MRA using pulsatile flow phantoms and human subjects, (2) To develop and test dynamic 4D VFA-FSE imaging that incorporates variable trigger delay and variable flow-spoiling for improved infragenual vessel evaluation and (3) To test prospectively an optimized 3 station VFA-FSE protocol with infragenual 4D VFA-FSE in 200 PAD patients, and to demonstrate comparable accuracy with bolus-chase and Gd-MRA and infragenual time-resolved Gd-MRA. The overarching goals of our research are to develop and validate a robust and artifact-free ECG-triggered variable flip angle FSE technique for peripheral MRA that provides accurate depictions of anatomy and disease without exposing patients to an exogenous contrast agent and its associated risks. Secondarily, we propose to explore dynamic 4D VFA-FSE acquisitions to produce time-resolved-like MRA images, and assess their accuracy for depicting complex flow patterns in infragenual vessels. PUBLIC HEALTH RELEVANCE: Given the risks and costs associated with gadolinium contrast material, the goal of our proposal is to develop a an accurate, efficient, and robust technique for non-contrast-enhanced peripheral MRA with advantages of obviating exogenous contrast material and reducing costs.